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BACKGROUND: Phenome-wide association studies (PheWASs) have been conducted on Asian populations, including Koreans, but many were based on chip or exome genotyping data. Such studies have limitations regarding whole genome-wide association analysis, making it crucial to have genome-to-phenome association information with the largest possible whole genome and matched phenome data to conduct further population-genome studies and develop health care services based on population genomics. RESULTS: Here, we present 4,157 whole genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest genomic resource of the Korean Genome Project. It encompasses most of the variants with allele frequency >0.001 in Koreans, indicating that it sufficiently covered most of the common and rare genetic variants with commonly measured phenotypes for Koreans. Korea4K provides 45,537,252 variants, and half of them were not present in Korea1K (1,094 samples). We also identified 1,356 new genotype-phenotype associations that were not found by the Korea1K dataset. Phenomics analyses further revealed 24 significant genetic correlations, 14 pleiotropic associations, and 127 causal relationships based on Mendelian randomization among 37 traits. In addition, the Korea4K imputation reference panel, the largest Korean variants reference to date, showed a superior imputation performance to Korea1K across all allele frequency categories. CONCLUSIONS: Collectively, Korea4K provides not only the largest Korean genome data but also corresponding health check-up parameters and novel genome-phenome associations. The large-scale pathological whole genome-wide omics data will become a powerful set for genome-phenome level association studies to discover causal markers for the prediction and diagnosis of health conditions in future studies.
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Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Humanos , Fenótipo , Estudos de Associação Genética , Frequência do Gene , República da Coreia , GenótipoRESUMO
Background and Purpose: Voice, reflecting cerebral functions, holds potential for analyzing and understanding brain function, especially in the context of cognitive impairment (CI) and Alzheimer's disease (AD). This study used voice data to distinguish between normal cognition and CI or Alzheimer's disease dementia (ADD). Methods: This study enrolled 3 groups of subjects: 1) 52 subjects with subjective cognitive decline; 2) 110 subjects with mild CI; and 3) 59 subjects with ADD. Voice features were extracted using Mel-frequency cepstral coefficients and Chroma. Results: A deep neural network (DNN) model showed promising performance, with an accuracy of roughly 81% in 10 trials in predicting ADD, which increased to an average value of about 82.0%±1.6% when evaluated against unseen test dataset. Conclusions: Although results did not demonstrate the level of accuracy necessary for a definitive clinical tool, they provided a compelling proof-of-concept for the potential use of voice data in cognitive status assessment. DNN algorithms using voice offer a promising approach to early detection of AD. They could improve the accuracy and accessibility of diagnosis, ultimately leading to better outcomes for patients.
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Red ginseng (RG) is a popular ingredient in traditional Korean medicine that has various health benefits. It is commonly taken orally as a dietary supplement; however, its potential interactions with concomitantly administered drugs are unclear. In this study, we examined the pharmacokinetic interaction between furosemide and RG in equine plasma. Liquid chromatography with tandem mass spectrometry analysis was performed to evaluate ginsenosides in the plasma of horses after feeding them RG and furosemide and validate the results. A single bolus of furosemide (0.5 mg/kg) was administered intravenously to female horses that had consumed RG (600 mg/kg/day) every morning for 3 weeks (experimental group), and blood samples were collected from 0 to 24 h, analyzed, and compared with those from female horses that did not consume RG (control group). Four (20s)-protopanaxadiol ginsenosides (Rb1, Rb2, Rc, and Rd) were detected in the plasma. Rb1 and Rc individually showed a high concentration distribution in the plasma. The Cmax, AUC0-t, and AUC0-∞ of furosemide was significantly increased in the experimental group (p < 0.05), while the CL, Vz, and Vss was decreased (p < 0.05, p < 0.01). These changes indicate the potential for pharmacokinetic interactions between furosemide and RG.
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Background: Acute myocardial infarction (AMI) is one of the leading causes of death worldwide, and approximately half of AMI-related deaths occur before the affected individual reaches the hospital. The present study aimed to identify and validate genetic variants associated with AMI and their role as prognostic markers. Materials and methods: We conducted a replication study of 29 previously identified novel loci containing 85 genetic variants associated with early-onset AMI using a new independent set of 2,920 Koreans [88 patients with early- and 1,085 patients with late-onset AMI, who underwent percutaneous coronary intervention (PCI), and 1,747 healthy controls]. Results: Of the 85 previously reported early-onset variants, six were confirmed in our genome-wide association study with a false discovery rate of less than 0.05. Notably, rs12639023, a cis-eQTL located in the intergenic region between LINC02005 and CNTN3, significantly increased longitudinal cardiac mortality and recurrent AMI. CNTN3 is known to play a role in altering vascular permeability. Another variant, rs78631167, located upstream of PLAUR and known to function in fibrinolysis, was moderately replicated in this study. By surveying the nearby genomic region around rs78631167, we identified a significant novel locus (rs8109584) located 13â bp downstream of rs78631167. The present study showed that six of the early-onset variants of AMI are applicable to both early- and late-onset cases. Conclusion: Our results confirm markers that can potentially be utilized to predict, screen, prevent, and treat candidate patients with AMI and highlight the potential of rs12639023 as a prognostic marker for cardiac mortality in AMI.
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In this study, 3D-printable flexible piezoresistive composites containing various amounts of cilia-like hybrid fillers were developed. In the hybrid fillers, micro-scale Cu particles with a 0D structure may allow them to easily disperse into the flexible TPU matrix. Furthermore, nanoscale multi-walled carbon nanotubes (MWCNTs) with a high aspect ratio, present on the surface of the Cu particles, form an electrical network when the polymer matrix is strained, thus providing good piezoresistive performance as well as good flowability of the composite materials. With an optimal hybrid filler content (17.5 vol.%), the 3D-printed piezoresistive composite exhibits a gauge factor of 6.04, strain range of over 20%, and durability of over 100 cycles. These results highlight the potential applications of piezoresistive pressure sensors for health monitoring, touch sensors, and electronic skin.
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We investigated the reinforcing effect of supersaturated Al-C phases on the mechanical properties of Al/C60 composites produced via powder metallurgy followed by thermal treatment. We controlled the fractions of C60-fullerenes, nano-scale carbides, and Al-C supersaturated phases in the Al/C60 composites by adjusting the heat-treatment temperature and duration. Furthermore, we examined the contribution of each phase on the elastic and plastic behavior of the composites using scanning acoustic microscopy (SAM) and hardness measurements. After heat treatment, a supersaturated Al-C phase and an Al carbide were formed in the Al/C composites by decomposition of individually dispersed C60. This led to enhancement of the hardness and elastic modulus of the Al/C composites heat-treated at 450 and 500 °C, while these properties were reduced in the 650 °C heat-treated composite. Notably, the 500 °C heat-treated composites showed significantly high hardness and elastic modulus (approximately 250 Hv and 77.8 GPa, respectively) owing to the substantially large contribution of the supersaturated Al-C phases, which was theoretically calculated to be 851 GPa/vol% and 227 GPa/vol%, respectively. This is possibly because the well-dispersed C in the atomic scale changed the elastic bonding characteristics of the metallic bonds between the Al atoms.
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Recently, the development of medical rehabilitation technology has resulted in an increased interest in speech therapy equipment. In particular, research on articulation therapy for communication disorders is being actively conducted. The existing methods for the diagnosis and treatment of speech disorders, such as traditional tactile perception tests and methods based on the empirical judgment of speech therapists, have many limitations. Moreover, the position and contact force of the tongue are key factors in speech disorders with regards to articulation. This is a very important factor in the distinction of Korean characters such as lax, tense and aspirated consonants. In this study, we proposed a Korean-electropalatography (EPG) system to easily measure and monitor the position and contact force of the tongue during articulation treatment and diagnosis. In our proposed K-EPG system, a sensor was fabricated using an AgCl electrode and biocompatible silicon. Furthermore, the measured signal was analyzed by implementing a bio-signal processing module and monitoring program. In particular, the bio-signal was measured by inserting the device into the palate of an experimental healthy test group (four subjects). Through these experiments, we confirmed that our K-EPG system could be applied to clinical treatment in speech therapy.
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Transtornos da Articulação , Fonoterapia , Humanos , Palato , República da Coreia , LínguaRESUMO
Purpose: To evaluate the accuracy of MRI in predicting the pathological complete response (pCR) and the residual tumor size of breast cancer after neoadjucant chemotherapy (NAC), and to determine the factors affecting the accuarcy. Materials and Methods: Eighty-eight breast cancer patients who underwent surgery after NAC at our center between 2010 and 2017 were included in this study. pCR was defined as the absence of invasive cancer on pathological evaluation. The maximum diameter of the residual tumor on post-NAC MRI was compared with the tumor size of the surgical specimen measured pathologically. Statistical analysis was performed to elucidate the factors affecting pCR and the residual tumor size-discrepancy between the MRI and the pathological measurements. Results: The pCR rate was 10%. The diagnostic accuracy of MRI and the area under the curve for predicting pCR were 90.91% and 0.8017, respectively. The residual tumor sizes obtained using MRI and pathological measurements showed a strong correlation (r = 0.9, p < 0.001), especially in patients with a single mass lesion (p = 0.047). The size discrepancy between MRI and the pathological measurements was significantly greater in patients with the luminal type (p = 0.023) and multifocal tumors/non-mass enhancement on pre-NAC MRI (p = 0.047). Conclusion: MRI is an accurate tool for evaluating pCR and residual tumor size in breast cancer patients who receive NAC. Tumor subtype and initial MRI features affect the accuracy of MRI.
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Two-dimensional (2D) semiconductors, such as transition-metal dichalcogenides (TMDs), have attracted immense interest due to their excellent electronic and optical properties. The combination of single and multilayered 2D TMDs coupled with either Si or II-VI semiconductors can result in robust and reliable photodetectors. In this paper, we report the deposition process of MoSe2-layered films using pulsed laser deposition (PLD) over areas of 20 cm2 with a tunable band gap. Raman and X-ray diffraction indicates crystalline and highly oriented layered MoSe2. X-ray photoelectron spectroscopy shows Mo and Se present in the first few layers of the film. Rutherford backscattering demonstrates the effect of O and C on the surface and film/substrate interface of the deposited films. Ultraviolet-visible spectroscopy, Kelvin probe, photoelectron spectroscopy, and electrical measurements are used to investigate the band diagram and electrical property dependence as a function of MoSe2 layers/thickness. As the MoSe2 thickness increases from 3.5 to 11.4 nm, the band gap decreases from 1.98 to 1.75 eV, the work function increases from 4.52 to 4.72 eV, the ionization energy increases from 5.71 to 5.77 eV, the sheet resistance decreases from 541 to 56.0 kΩ, the contact resistance decreases from 187 to 54.6 Ω·cm2, and the transfer length increases from 2.27 to 61.9 nm. Transmission electron microscopy (TEM) cross-sectional images demonstrate the layered structure of the MoSe2 with an average interlayer spacing of 0.68 nm. The fabricated MoSe2-Si photodiodes demonstrate a current on/off ratio of â¼2 × 104 orders of magnification and photocurrent generation with a 22.5 ns rise time and a 190.8 ns decay time, respectively.
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Metal matrix composites (MMCs) are promising alternatives to metallic alloys. Their high strength-to-weight ratios; high temperature stabilities; and unique thermal, electrical, and chemical properties make them suitable for automotive, aerospace, defense, electrical, electronic, energy, biomedical, and other applications. The wide range of potential combinations of materials allows the properties of MMCs to be tailored by manipulating the morphology, size, orientation, and fraction of reinforcement, offering further opportunities for a variety of applications in daily life. This Special Issue, "Metal Matrix Composites", addresses advances in the material science, processing, material modeling and characterization, performance, and testing of metal matrix composites.
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The nitridation-induced self-formed aluminum matrix composite (NISFAC) process is based on the nitridation reaction, which can be significantly influenced by the characteristics of the starting materials (e.g., the chemical composition of the aluminum powder and the type, size, and volume fraction of the ceramic reinforcement) and the processing variables (e.g., process temperature and time, and flow rate of nitrogen gas). Since these variables do not independently affect the nitridation behavior, a systematic study is necessary to examine the combined effect of these variables upon nitridation. In this second part of our two-part report, we examine the effect of nitrogen flow rates and processing temperatures upon the degree of nitridation which, in turn, determines the amount of exothermic reaction and the amount of molten Al in the nitridation-induced self-formed aluminum matrix composite (NISFAC) process. When either the nitrogen flow rate or the set temperature was too low, high-quality composites were not obtained because the level of nitridation was insufficient to fill the powder voids with molten Al. Hence, since the filling of the voids in the powder bed by molten Al is essential to the NISFAC process, the conditions should be optimized by manipulating the nitrogen flow rate and processing temperature.
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This paper investigates the effect of the size and volume fraction of SiC, along with that of the processing temperature, upon the nitridation behavior of aluminum powder during the nitridation-induced self-formed aluminum composite (NISFAC) process. In this new composite manufacturing process, aluminum powder and ceramic reinforcement mixtures are heated in nitrogen gas, thus allowing the exothermic nitridation reaction to partially melt the aluminum powder in order to assist the composite densification and improve the wetting between the aluminum and the ceramic. The formation of a sufficient amount of molten aluminum is key to producing sound, pore-free aluminum matrix composites (AMCs); hence, the degree of nitridation is a key factor. It was demonstrated that the degree of nitridation increases with decreasing SiC particle size and increasing SiC volume fraction, thus suggesting that the SiC surface may act as an effective pathway for nitrogen gas diffusion. Furthermore, it was found that effective nitridation occurs only at an optimal processing temperature. When the degree of nitridation is insufficient, molten Al is unable to fill the voids in the powder bed, leading to the formation of low-quality composites with high porosities. However, excessive nitridation is found to rapidly consume the nitrogen gas, leading to a rapid drop in the pressure in the crucible and exposing the remaining aluminum powder in the upper part of the powder bed. The nitridation behavior is not affected by these variables acting independently; therefore, a systematic study is needed in order to examine the concerted effect of these variables so as to determine the optimal conditions to produce AMCs with desirable properties for target applications.
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Metallic matrix composites reinforced with carbon nanomaterials continue to attract interest because of their excellent mechanical, thermal, and electrical properties. However, two critical issues have limited their commercialization. Uniform distribution of carbon nanomaterials in metallic matrices is difficult, and the interfaces between the nanomaterials and matrices are weak. Microscope-based analysis was recently used to quantitatively examine these microstructural features and investigate their contributions to the composites' mechanical, thermal, and electrical properties. The impacts of the microstructure on these properties are discussed in the first section of this review. In the second section, the various microscopic techniques used to study the distribution of carbon nanomaterials in metallic matrices and their interfaces are described.
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The aim of the present study was to evaluate programmed death-1 (PD-1) and programmed death-1 ligand-1 (PD-L1) expression in gastric carcinoma and to assess their effect on survival rate. A total of 170 surgically resected specimens were obtained from patients diagnosed with gastric carcinoma at St. Vincents Hospital, The Catholic University of Korea. Paraffin tissue sections from tissue microarray blocks were subjected to immunohistochemical analysis of PD-1 and PD-L1. In addition, PD-1 expression on CD4+ and CD8+ T cells isolated from peripheral blood mononuclear cells and gastric cancer tissues was evaluated by multicolor flow cytometry. PD-1 and PD-L1 were expressed in 30.0 and 60.5% of the gastric cancer tissues, respectively. The expression of PD-L1 was higher in patients with advanced T (P=0.035) and Tumor, Node and Metastasis stage (P=0.05). The patients with positive PD-L1 expression had shorter disease-free survival time than those without PD-L1 expression (P=0.005). Additionally, PD-L1 expression was significantly associated with poor prognosis (P=0.015). PD-1 and PD-L1 expression levels were significantly higher on CD8+ T cells than on CD4+ T cells (P<0.001). The data of the present study suggested that PD-L1 expression may be an independent indicator of poor prognosis in patients with gastric cancer. Furthermore, PD-L1 expression may play a role in immune evasion of gastric cancer.
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Conventional manufacturing processes for aluminum matrix composites (AMCs) involve complex procedures that require unique equipment and skills at each stage. This increases the process costs and limits the scope of potential applications. In this study, a simple and facile route for AMC manufacturing is developed, a mixture of Al powder and the ceramic reinforcement is simply heated under nitrogen atmosphere to produce the composite. During heating under nitrogen atmosphere, the surface modification of both Al and the reinforcement is induced by nitridation. When the oxide layer covering Al powder surface is transformed to nitrides, temperature in the local region increases rapidly, resulting in a partial melt of Al powder. The molten Al infiltrates into the empty space among Al powder and reinforcement, thereby enabling consolidation of powders without external forces. It is possible to fabricate AMCs with various types, sizes, volume fractions, and morphologies of the reinforcement. Furthermore, the manufacturing temperature can be lowered below the melting point of Al (or the solidus temperature for alloys) because of the exothermic nature of the nitridation, which prevents formation of un-wanted reactants. The relative simplicity of this process will not only provide sufficient price competitiveness for the final products but also contribute to the expansion of the application scope of AMCs.
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While nanocrystalline (NC) metals exhibit superior strength to conventional microcrystalline metals, their thermal instability has hampered their application at high temperatures. Herein, two-dimensional (2D) boron nitride nanosheets (BNNS) are proposed as reinforcement to enhance the strength as well as the thermal stability of NC Al. The strength of pure Al was increased from 80 to 468 MPa by refining its grains from ~600 to ~40 nm, and it was further enhanced to 685 MPa by incorporating 2 vol% of BNNS. Moreover, the small amount of BNNS was found to effectively suppress grain growth of NC Al at 580 °C (~0.9 Tm, where Tm is the melting point of Al), which prevented a strength drop at high temperature. Finally, the Zener pinning model in conjunction with phase-field simulations was utilized to qualitatively analyze the effect of the BNNS on the grain boundary pinning as a function of volume, shape, and orientation of the reinforcement. The model demonstrated that the pinning force of 2D reinforcements is much higher than that of spherical particles. Hence, 2D BNNS offer the possibility of developing Al-matrix nanocomposites for high-temperature structural applications.
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A scalable and catalyst-free method to deposit stoichiometric molybdenum disulfide (MoS2) films over large areas is reported, with the maximum area limited by the size of the substrate holder. The method allows deposition of MoS2 layers on a wide range of substrates without any additional surface preparation, including single-crystal (sapphire and quartz), polycrystalline (HfO2), and amorphous (SiO2) substrates. The films are deposited using carefully designed MoS2 targets fabricated with excess sulfur and variable MoS2 and sulfur particle size. Uniform and layered MoS2 films as thin as two monolayers, with an electrical resistivity of 1.54 × 10(4) Ω cm(-1), were achieved. The MoS2 stoichiometry was confirmed by high-resolution Rutherford backscattering spectrometry. With the method reported here, in situ graded MoS2 films ranging from â¼1 to 10 monolayers can be deposited.
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Few studies have investigated language recovery patterns and the mechanisms of crossed bilingual aphasia following a subcortical stroke. In particular, Korean-Japanese crossed bilingual aphasia has not been reported. A 47-year-old, right-handed man was diagnosed with an extensive right basal ganglia hemorrhage. He was bilingual, fluent in both Korean and Japanese. After his stroke, the patient presented with crossed aphasia. We investigated changes in the Korean (L1) and Japanese (L2) language recovery patterns. Both Korean and Japanese versions of the Western Aphasia Battery (WAB) were completed one month after the stroke, and functional magnetic resonance imaging (fMRI) was performed using picture-naming tasks. The WAB showed a paradoxical pattern of bilingual aphasia, with an aphasia quotient (AQ) of 32 for Korean and 50.6 for Japanese, with Broca's aphasia. The patient scored better in the Japanese version of all domains of the tests. The fMRI study showed left lateralized activation in both language tasks, especially in the inferior frontal gyrus. After six months of language therapy targeting L1, the Korean-WAB score improved significantly, while the Japanese-WAB score showed slight improvement. In this case, the subcortical lesion contributed to crossed bilingual aphasia more highly affecting L1 due to loss of the cortico-subcortical control mechanism in the dominant hemisphere. The paradoxical pattern of bilingual aphasia disappeared after lengthy language therapy targeting L1, and the therapy effect did not transfer to L2. Language recovery in L1 might have been accomplished by reintegrating language networks, including the contralesional language homologue area in the left hemisphere.
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Afasia de Broca/fisiopatologia , Hemorragia dos Gânglios da Base/complicações , Multilinguismo , Afasia de Broca/diagnóstico por imagem , Afasia de Broca/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: With thyroid carcinoma the decision to use radioactive iodine (RAI) ablation depends on the risk of poor outcomes. Although extrathyroid extension (ETE) is well known as a risk of poor outcomes for papillary thyroid carcinoma (PTC), the definition of minimal ETE is too broad, as it encompasses both microscopic invasion of the thyroid capsule (capsular invasion [CI]) and macroscopic invasion of the sternothyroid muscle. METHODS: We conducted a retrospective study to analyze the prognostic benefit of RAI ablation according to the presence of CI in a consecutive series of patients with PTC between October 1997 and December 2008. We studied two groups of patients, including those who received RAI (group I, n = 121) and those who did not (group II, n = 108). During follow-up, we assessed the locoregional recurrence of all patients. RESULTS: There were no statistically significant difference between the groups regarding locoregional recurrence at follow-up (13.2% for group Iâ vs 9.3% for group II, P = 0.441). The association between RAI and locoregional recurrence in PTC patients with CI remained insignificant after adjusting for potential confounders, such as age, tumor size, sex, lymphatic invasion, vascular invasion and tumor multiplicity (P = 0.409, hazard ratio = 0.698, 95% confidence interval, 0.298-1.639). CONCLUSIONS: This retrospective study suggests that RAI treatment is not associated with less locoregional recurrence in PTC patients who only demonstrate CI, although further prospective studies are required to confirm these findings.
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Antineoplásicos/uso terapêutico , Carcinoma/radioterapia , Radioisótopos do Iodo/uso terapêutico , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Glândula Tireoide/radioterapia , Adulto , Carcinoma Papilar , Feminino , Humanos , Iodo , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Câncer Papilífero da TireoideRESUMO
BACKGROUND: The high mobility group A1 (HMGA1) and high mobility group A2 (HMGA2) proteins are architectural transcription factors that have been implicated in the pathogenesis and progression of multiple malignant tumors, including gastric cancer. The aim of this study was to explore the roles of HMGA1 and HMGA2 in gastric carcinogenesis. METHODS: The expression of HMGA1 and HMGA2 was examined in 110 gastric adenocarcinomas, 29 gastric adenomas, and 30 normal controls. The results were correlated with the clinicopathological parameters of the tumors and patient outcome. RESULTS: The levels of HMGA1 and HMGA2 proteins were significantly increased in gastric cancer samples compared with adenoma and normal gastric tissues. High HMGA1 nuclear immunoreactivity was not correlated with clinicopathological features; however, high levels of HMGA2 protein were significantly associated with T stage, N stage, lymphatic invasion, perineural invasion, and TNM stage. Moreover, HMGA2 expression was significantly associated with shorter recurrence free survival. Multivariate analysis showed that HMGA2 expression was an independent prognostic factor for tumor recurrence. CONCLUSIONS: Our results suggest that HMGA1 and HMGA2 are implicated in gastric carcinogenesis and may play a role in tumor progression towards a more malignant phenotype. The HMGA2 protein may be a useful prognostic marker for predicting tumor recurrence.